The goal of this project is to characterize mechanisms of immunoregulation of antibody synthesis and secretion, particularly Ir genes and idiotype networks. Recently, a system has been developed in which, for the first time, soluble antibody responses to the synthetic polypeptide (T,G)-A--L can be generated and detected in vitro using antigen-primed lymph node cells. Responses are antigen dependent and specific, and H-2 linked Ir gene regulated. Antibodies specific for the idiotypes of anti-(T,G)-A--L antibodies induce antigen-independent anti-(T,G)-A--L antibody responses. These responses are specific at the levels of the anti-idiotype reagent, the antigen-priming, and the antibody produced. The anti-idiotype antibodies stimulate function from antigen-primed T lymphocytes in the form of soluble lymphokines, and function from both primed and unprimed B cells in the form of specific antibody secretion. Unprimed B cells, in addition to anti-idiotype, require either primed T cells or idiotype present in order to obtain function. Responses to anti-idiotype antibodies, in contrast to those to antigen, appear not to be regulated by Ir genes.